Protein dynamics in the solid state

Protein dynamics in the solid state

Over 40000 unique protein structures have been determined by X-ray crystallography, yet little information is available concerning their dynamic behaviour. Solid state NMR can provide atomic resolution information about protein motions occurring on a vast range of timescales under similar conditions to X-ray diffraction studies, and therefore offers a highly complementary approach to characterizing the dynamic fluctuations occurring in the crystal. In collaboration with the Prof. Lyndon Emsley (ENS, Lyon) we develop experimental NMR tools for probing site-specific dynamics in the solid state for example using experiments for measuring 13C relaxation rates as well as for probing slow micro- to millisecond motions. In addition to the experimental developments, we provide analytical tools for the detection of collective motions in the solid state.
In addition to the development of experimental and analytical tools, we also make use of molecular dynamics simulations by simulating multiple explicit copies of the proteins representing the crystalline lattice (Figure 1). In combination these approaches provide a unique description of protein dynamics in the solid state, and allow comparison of motional modes and amplitudes over a large range of timescales with those observed in solution on the same systems.

Figure 1. Comparison of experimentally determined dynamic parameters, spin relaxation, chemical shifts and dipolar couplings, to values calculated from a 200ns molecular dynamics simulation of protein GB1 in its crystalline form. We provide novel insight into the averaging of NMR parameters in microcrystalline proteins and develop a unique description of structural dynamics occurring within the crystalline lattice.